化疗引起的恶心呕吐的预防与管理.ppt

Evidence,ChallengesandSolutions:PreventingandManagingChemotherapy-InducedNauseaandVomiting,ScottEdwards,PharmDClinicalOncologyPharmacistEasternHealth,St.Johns,NLNOPS2019,PatientPerceptionsoftheMostSevereSideEffectsofCancerChemotherapy,Adaptedfrom:1CoatesAetal.EurJCancerClinOncol.1983;19:203-8.2GriffinAMetal.AnnOncol.2019;7:189-95.3DeBoer-DennertMetal.BrJCancer.2019;76:1055-61.4LindleyCetal.CancerPract2019;7:59-65.,CINV-Definitions,Acutewithinafewminutestoseveralhoursafterdrugadministrationandcommonlyresolveswithin24hours.Delayeddevelopsinpatientsmorethan24hoursafterchemotherapyadministration.Maylastupto6daysItcommonlyoccurswithcisplatin,carboplatin,cyclophosphamideand/oranthracyclines.Anticipatorynauseaand/orvomitingbeforepatientsreceivetheirchemotherapy,afterapriornegativeexperiencewithchemotherapyBreakthroughoccursdespiteprophylactictreatmentand/orrequiresrescue.Refractorynauseaandemesisduringsubsequentcycleswhenantiemeticprophylaxisand/orrescuehavefailedinearliercycles,Adaptedfrom:ASHPAmJHealthSystPharm2019;56:729-764NCCNPracticeGuidelinesinOncologyVersion3.2019.Antiemesis,RatesofCINV,Adaptedfrom:1.HickokJT,etal.Cancer.2019;97:2880-6.2.ashpadvantage/previous_meetings/mcm_2019/cemornings2019/CEM_CINV_handout.pdf,Chemotherapy-InducedEmesisRiskFactors,Patient-relatedriskfactorsinclude:YoungerageFemalegenderNo/minimalpriorhistoryofalcoholusePriorCINVAnxietyHighpretreatmentexpectationofseverenausea,Adaptedfrom:GregoryREetal.Drugs.2019.;2.HeskethPJetal.JClinOncol.2019.RoscoeJA,BushunnowP,MorrowGR,etal.Patientexperienceisastrongpredictorofseverenauseaafterchemotherapy:aUniversityofRochesterCommunityClinicalOncologyProgramstudyofpatientswithbreastcarcinoma.Cancer2019;101:2701-2708,InfluenceofPatientExpectationsonCINV,Expectancyofnauseaassessedbeforepatientsreceivedtheirfirstdoxorubicin-basedchemotherapytreatmentwasfoundtobeastrongpredictorofsubsequentnausea.,AdaptedfromRoscoeetal.Cancer.2019101(11):2701-8.,Chemotherapy-InducedEmesisRiskFactors,Treatment-relatedriskfactorsinclude:HighdrugdoseHighemetogenicityofchemotherapydrugsOfalltheknownpredictivefactors,theemetogenicityofagivenchemotherapeuticagentisthepredominantfactor.,AdaptedfromASHPAmJHealthSystPharm2019;56:729-64.,CausesofCINV,Inadditiontoemesisinducedbychemotherapy,CINVcanbecausedby:PartialorcompletebowelobstructionVestibularDysfunctionBrainMetastasesElectrolyteimbalance:hypercalcemia,hyperglycemia,hyponatremia,uremiaConcomitantdrugs,includingopiatesGastroparesisinducedbyatumororchemotherapy(suchasvincristine)Psychophysiologicfactors,includinganxietyaswellasanticipatorynauseaandvomiting,AdaptedfromNCCNPracticeGuidelinesinOncologyVersion3.2019.Antiemesis.,ConsequenceofUnresolvedCINV,DiscontinuationoftherapySeriousmetabolicderangementsNutritionaldepletionandanorexiaEsophagealtearsWounddehiscenceDeteriorationofpatientsphysicalandmentalstatusDegenerationofself-careandfunctionalability,Adversesequelaeofnauseaandvomitinginthecancerpatient.,AdaptedfromNCCNPracticeGuidelinesinOncologyVersion3.2019.Antiemesis.,PolloftheaudienceAsHealthcareprofessionalsweoften:,A.AccuratelyrecognizetheincidenceofacuteanddelayedCINVinourownpractices.B.UnderestimatetheincidenceofacuteanddelayedCINVinourownpractices.,AntiNauseaChemotherapyRegistry(ANCHOR)study,TheauthorsdeterminedtheincidenceofacuteanddelayedCINVaftermodernantiemetics.ThentheycomparedtheactualincidencesofCINVtothepredictionsmadebyphysiciansandnursesregardingthesepatients.,AdaptedfromGrunbergSMetal.Cancer2019;100:2261-8.,AnchorStudyPerceptionvsRealityModeratelyEmetogenicChemotherapy,AdaptedfromGrunbergetal.Cancer2019;100:2261-8.,ToxicityAssessments,Gradecommontoxicityeffectsofadjuvantbreastcancerpatients.Patientsareassessedthedayofchemotherapyandagain2-3dayspostchemotherapy.Patientsalsohaveanumbertocallbackiftheyexperienceanytoxicities.,Dr.H.BlissMurphyCancerCenter,St.JohnsNewfoundland,RatesofCINVin,N=26,Dr.H.BlissMurphyCancerCenter,St.JohnsNewfoundland,RateofCINV,AdaptedfromCancer2019;100:2261-8.,N=231,attheDr.H.BlissMurphyCancerCenter,St.JohnsNewfoundlandincomparisontotheGrunbergdata,HealthCareProfessionalsPerceptionofCINVattheDr.H.BlissMurphyCancerCenter,St.JohnsNewfoundland,AdaptedfromCancer2019;100:2261-8.,CINVDecreasedQualityofLife,CINVadverselyimpactpatientsqualityoflife.OvariancancerpatientsinarecentstudyincludedcompletetoalmostcompletecontrolfromCINVamongthemostfavorablehealthstates,justbelowperfecthealthandclinicalremission.,AdaptedfromSupportCareCancer2019;13:219-27.,CINVDecreasedQualityofLife,AdaptedfromSupportCareCancer2019;13:219-27.,AdaptedfromBloechl-DaumBetal.JClinOncol.2019;24:4472.,CINVDecreasedQualityofLife,FLIEQuestionnaireHEC-FLIEMEC-FLIEP=0.0049FLIE-nauseaFLIE-VomitingP=0.0097ThereisagreaternegativeimpactonQOLfromnauseathanthereisfromvomitingThereisagreaternegativeimpactonQOLfromHECthanthereisfromMEC,FLIE=FunctionalLivingIndex-Emesis;HEC=highlyemetogenicchemotherapy;MEC=moderatelyemetogenicchemotherapy.,SummaryoftheImportanceofPreventionandTreatmentofCINV,TherestillisahighlevelofanguishforCINVexperiencedbyourpatients.Ashealthcareprofessionals,wemaynotbeaccuratelypredictingthelevelofCINVexperiencedbyourpatients.CINVhasaenormousimpactonourpatientsqualityoflife.,MechanismsofCINV,Centralmechanism:Chemotherapeuticagentactivatesthechemoreceptortriggerzone(CTZ).ActivatedCTZinvokesreleaseofvariousneurotransmitters,whichstimulatevomitingcenter.Peripheralmechanism:Chemotherapeuticagentcausesirritationanddamagetogastrointestinal(GI)mucosa,resultinginthereleaseofneurotransmitters.Activatedreceptorssendsignalstovomitingcenterviavagalafferents.,Adaptedfrom:BergerAMetal.In:Cancer:PrinciplesandPracticeofOncology.6thed.LippincottWilliams2019:28692880.,AdaptedfromNEnglJMed2019;358:2482-94.,Serotoninand5-HT3ReceptorPathway,Firstrecognizedwithhigh-dosemetoclopramide.Developmentof5-HT3antagonistshashaddramaticimpact:Highlyeffectiveinacutevomiting,lesseffectivefordelayedevents.Optimaluseiswithdexamethasone.Primarymechanismofactionappearstobeperipheral.,Adaptedfrom:BergerAMetal.In:Cancer:PrinciplesandPracticeofOncology.6thed.LippincottWilliams39:1074-80.,SubstancePandNeurokinin1(NK1)ReceptorPathway,HighdensityofsubstanceP/NK1receptorslocatedinbrainregionsimplicatedintheemeticreflex.PrimarymechanismofNK1receptorblockadeactionappearstobecentral.Effectiveforbothacuteanddelayedevents.Augmentsantiemeticactivityofa5-HT3receptorantagonistandcorticosteroid.,Adaptedfrom:HargreavesRJClinPsychiatry2019;63(suppl11):18-24.SariaAEurJPharmacol2019;375:51-60.HeskethPJSupportCareCancer2019;9:350-54.,ConceptualModelofAcute20:113.2.MorrowGR,etal.SupportCareCancer2019;6:244.,AnticipatoryCINV,Anticipatorynauseaand/orvomitingistheoccurrenceofnauseaand/orvomitingbeforepatientsreceivetheirchemotherapytreatment.Becauseitisaconditionedresponse,itcanonlyoccurafteranegativepastexperiencewithchemotherapy.Challenge-Anticipatorynauseaand/orvomitingoccursin18%to57%ofchemotherapypatients.Youngerpatientsmaybemoresusceptibleastheygenerallyreceivemoreaggressivetherapyandhavepooreremesiscontrolthanolderpatients.,AnticipatoryCINV(continued),ThemosteffectivewaytotreatistopreventCINVbyusingoptimalantiemeticsduringeverycycleoftherapy.Either:AlprazolamPO0.25to0.5mgt.i.d.beginningonthenightbeforetreatmentOR;Lorazepam0.5-2mgPOonthenightbeforeandthemorningoftreatment.BehavioraltherapySystemicdensensitization,AdaptedfromNCCNPracticeGuidelinesinOncologyVersion3.2019.Antiemesis,AdaptedfromGrunbergetal.Cancer2019;100:2261.,DelayedCINV,Challenge-Delayedemesisis2.5timesmoreprevalentthanacuteemesis.Formoderatelyemetogenicchemotherapy:Delayednauseaexceedsacutenauseaby16%.Delayedemesisexceedsacuteemesisby15%.Forhighlyemetogenicchemotherapy:Delayednauseaexceedsacutenauseaby27%.Delayedemesisexceedsacuteemesisby38%.,PrognosticFactorsforDelayedCINV,Strongestpredictorofdelayednauseaandvomitingwastheoccurrenceofacutenauseaandvomiting.Patientsaged52yearsoryoungerandwomenweremorelikelytohavedelayednauseathanwerethoseolderthan52yearsandmen.Ahighexpectationofnauseawasasignificantpredictorofmoreseverenausea.,AdaptedfromTheLancetOncologyOctober2019;Vol(6):Issue(10):765-72.,Case1,InitialPresentationMaryT.isa56-year-oldfemalewhowascompletelyasymptomaticwhenaroutinemammogramshowedtwolesions.Sheunderwentdiagnostictestingandhadamastectomyandauxiliarylymphnodedissection.DiagnosisT3(morethan5cm)N0(0/6lymphnodes)M0.poorlydifferentiatedinvasiveductalcarcinomaofrightbreast,ER/PRpositiveandHER-2/neunegative.,InitialPresentation,PASTMEDICALHISTORY:Unremarkable.SOCIALHISTORY:Schoolteacher,married,motheroftwogrownchildrenlivingaway,nonsmoker,occasionaldrinkontheweekends.MEDICATIONS:Ranitidine150mgb.i.d.,Lorazepam1mgprnSYSTEMINQUIRY:Unremarkable.Allergies:NKA(drugs,food,environmentalallergens),FirstCycleofChemotherapy(FEC),ThepatientisprescribedFEC(Fluorouracil,Epirubicin,Cyclophosphamide)for3cyclesfollowedbyTaxoterefor3cycles.ShewasgivenOndansetron8mgandDexamethasone8mgpriortoherfirstcycleofchemotherapy.ShewasgivenaprescriptionforOndansetron8mgandDexamethasone4mgpob.i.d.x2dayspostchemotherapyaswellasMetoclopramide10mgpoq6hprntobetakenpostchemotherapy.,NauseapostCycle1,Whenshereturnedforcycletwosheinformedthepharmacistthatshehadvomitedonday2andthatshehadexperiencednauseafordays2-5postchemotherapy.Sheratesthisnauseaasa8/10fordays2-4and6/10forday5.,Case1:Question1,Whatanti-emeticswouldyourecommendtobegivenpriortochemotherapyforhersecondcycleofFEC?Metoclopramide10mgOndansetron8mg,Dexamethasone8mgandAprepitant125mgOndansetron8mgandDexamethasone8mg,Womenreceivingacombinationofanthracycline+cyclophosphamiderepresentasituationwithaparticularlygreatriskofvomitingandnausea.Topreventacutevomitingandnauseainthesewomen,athree-drugregimenincludingsingledosesof:5-HT3antagonistDexamethasoneAprepitant(orfosaprepitant)givenbeforechemotherapyisrecommended.,AdaptedfromMASCCAntiemeticMarch2019GuidelineUpdate.,AnswerQuestion1=BGuidelineforthePreventionofAcuteNauseaandVomitingFollowingChemotherapyofModerateEmeticRisk(MEC):,Case1:Question2,Whatanti-emeticswouldbeofferedtothispatientasananti-nauseatakehomeprescriptionfortheFEC(cycle2)regimen?A.Dexamethasone8mgbidx3daysandMetoclopramide10mgq6hprn.B.Metoclopramide10mgq6hprn.C.Aprepitant80mgondays2and3,Ondansetron8mgandDexamethasone4mgbidx2daysandMetoclopramide10mgq6hprn.,AnswerQuestion2,Adaptedfrombccancer.bc.ca.,Case1:Question3,WhatotheractionscanthepharmacisttaketohelpM.T.controlherCINV?,AnswerQuestion3,Explorepatientadherencewithanti-emetics.Assesseffectiveness/ineffectivenessofanti-emeticplan.Followuptoxicityassessments(useCCOtelephonetoxicityguidelines).CINVeducation.Communicationwithherotherhealthcareproviders.Patientnauseadiary(CANOpatienteducationforCINV).Promotepatientinvolvementthroughpatientresources:ChemotherapyandYou:AGuidetoSelf-HelpDuringCancerTreatment,/cancerinfo/chemotherapy-and-youcancernausea,Case1:Question4,Thepharmacistasksthepatientwhatmedicationssheiscurrentlytaking.SheinformsthenursesheistakingWarfarin,MetoprololandASA.ShouldshebeconcernedaboutadruginteractionwithWarfarinandAprepitant?,Case1:Question5,WhichofthefollowingmayoccurwiththeadditionofaprepitanttoM.Tsregimen?A.INRmaydeclineB.INRmayincreaseC.Warfarinlevelsmayrise,AnswerQuestion4and5WarfarinAprepitantInteraction,AprepitantisaCYP3A4substrate,a3A4inhibitorandinducer,anda2C9inducer.INRmaydecline.,AdaptedfromAprepitantMonograph.RetrievedJuly22,2019fromcancercare.on.ca/pdfdrugs/aprepitant.pdf,ImportanceofMedicationReconciliation,PilotProjectofMedicationReconciliationinSt.Johns,NewfoundlandCancerCenterSummerprojectPharmacyStudentsObtaininganaccuratemedicationhistoryforchemotherapypatients,TotalNumberofMedicationsvs.TotalNumberofInaccuraciesorOmissions,CancerCareProgram,Identificationofthenumberofpatientswithinaccuraciesoromissionsaswellasthenumberofdrugrelatedproblemsidentified,CancerCareProgram,IdentificationofthenumberofpatientswithinaccuraciesoromissionsaswellasthenumberofpatientstakingOTC/Herbals,CancerCareProgram,StartingDocetaxelafterFEC,M.T.completedherthreecyclesofFECaspartoftheFEC-Dregimen.SincetheadditionofAprepitant,hernauseacontrolhasbeenmuchbetter.SincesheisstartingDocetaxel,sheneedstotakeDexamethasone8mgpob.i.d.for3days,starting24hourspriortochemotherapy.ThemedicaloncologyteamwouldliketokeepM.T.onAprepitantduetoherimprovedresponse.,Case1:Question6,Astheoncologypharmacist,youtelltheteamthattheyneedtobeconcernedaboutAprepitantdruginteractions.WhichofthefollowingwouldbecorrecttotelltheteamaboutAprepitant:A.AprepitantisaSubstrateforCYP3A4,andModerateInhibitorofCYP3A4.B.AprepitantisaWeakInducerofCYP3A4andCYP2C9.C.BothAandBarecorrect.,AnswerQuestion6-AprepitantandP450,SubstrateforCYP3A4,CYP2C19andCYP1A2WeakInducerofCYP3A4andCYP2C9ModerateInhibitorofCYP3A4WeakinhibitorofCYP2C9andCYP2C19,Case1:Question7,ThegeneralrecommendationsfordosingdexamethasonewhencombinedwithAprepitantis:A.Reducethedoseofdexamethasoneby50%B.Increasethedoseofdexamethasoneby50%C.Donotadjustthedoseofdexamethasone,AnswerQuestion7,AprepitantincreasestheAUCofdexamethasonewhenthetwoareadministeredconcomitantly.Reducedexamethasonedoseby50%.,Case1:Question8,WhatwouldbeyourrecommendationsfordosingdexamethasoneforDocetaxelpremedicationwhencombinedwithAprepitantforM.T.:A.Reducethedoseofdexamethasoneby50%B.Increasethedoseofdexamethasoneby50%C.Donotadjustthedoseofdexamethasone,Case2,JimmyT.isaA27yearoldwithahistoryofT2N2M1a,StageIIInon-seminomatesticularcancer.Hehadsurgeryforthisandinfollowupwasfoundtohavemetastaticdisease.Hehadatleasttwolunglesionsaswellassomemediastinaladenopathyandretroperitonealadenopathy.,InitialPresentation,PASTMEDICALHISTORY:Unremarkable.SOCIALHISTORY:Heliveswithhiscommonlawgirlfriend,Occasionaldrinkonweekends,nonsmokerMEDICATIONS:AcetaminophenprnSYSTEMINQUIRY:Unremarkable.Allergies:NKA(drugs,food,environmentalallergens)a,Firstcycleofchemotherapy(BEP),ThepatientisprescribedBEP(BLEOMYCIN-ETOPOSIDE-CISPLATIN)Chemotherapyfor4cycles.,Case2:Question1,Whatanti-emeticswouldyourecommendtobegivenpriortochemotherapyforhisfirstcycleofBEP?Metoclopramide10mgprechemotherapyfor5daysOndansetron8mg,Dexamethasone8mgandAprepitant125mgonday1prechemotherapyandOndansetron8mg,Dexamethasone4mgandAprepitant80mgondays2-5prechemotherapyOndansetron8mgandDexamethasone8mgprechemotherapyondays1-5,AnswerQuestion1MultipleDayChemotherapy,A5-HT3receptorantagonistshouldbeadministeredpriortoeachdays1stdoseofmoderatelyorhighly-emetogenicchemotherapy.Dexamethasoneshouldbeadministeredoncedailyeitherorallyorivforeverydayofchemotherapyandfor2-3dayspostchemotherapy.Aprepitantmaybeusedformulti-daychemotherapy.Aprepitant125mgonday1,thenaprepitant80mgdailyondays2and3alongwithdexamethasone.BasedonPhaseIIdata,aprepitantmaybesafelyadministeredondays4and5afterchemotherapy.,AdaptedfromNCCNPracticeGuidelinesinOncologyVersion3.2019.Antiemesis,Case2:Question2,TheoncologypharmacistperformsatoxicityassessmentonJimmyT.3days(Mondayafternoon)postchemotherapy.ThepatientcomplainsofsignificantnauseathatstartedonSundayevening.Hevomitedx1onMondaymorning.Heratesthenauseaas8outof10.HestateshewasgivenaprescriptionforOndansetron8andDexame